(1S,4R)-cis-[2-Amino-6chloro-9H-purin-9-yl]-2-cyclopentene-1-methanol, the chloropurine compound of formula (I)
is described in European Patent No. 0 325 460 and can be used as an intermediate in the manufacture of abacavir ((1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol), a 2-aminopurine nucleoside compound of formula (II)

The antiviral use of abacavir, particularly in the treatment of the human immunodeficiency virus (HIV), is described in European Patent No. 0 434 450 and the hemisulfate salt of abacavir, described in International Patent Application No. WO98/52949, is commercially available from GlaxoSmithKdine for the treatment of HIV under the tradename ZIAGEN®.
Processes for preparing abacavir and intermediates useful in the synthesis of abacavir have been described by, for example, Daluge et al. in Nucleosides, Nucleotides & Nucleic Acids, 19 (1&2), 2000, 297-327. International Patent Application No. WO99/19327 describes an in situ process for the preparation of the chloropurine compound of formula (I) which comprises hydrolysing a compound of formula (III)
wherein P is a protecting group, in the presence of an acid, condensing the product of formula (IV) formed
in situ in the presence of a base with a compound of formula (V)
in which R represents CHO or H, followed by ring closure in situ of the resulting intermediate of formula (VI)

According to WO99/19327, the ring closure reaction is preferably carried out in the presence of from about 1.5 to 3 molar equivalents of hydrochloric acid and a large excess of triethylorthoformate, which results in precipitation of the hydrochloride salt of the chloropurine compound of formula (I).
As abacavir is sold as a prescription medicine for the treatment of HIV infections, there exists a need to develop more efficient processes for preparing the compound in large quantities.
We have now found a process for preparing the chloropurine compound of formula (I) or a derivative thereof in which the amount of both the acid and formate derivative used in the cyclisation step is significantly reduced. The process according to the present invention thus allows abacavir and derivatives thereof to be prepared without isolation of the highly toxic hydrochloride salt of the chloropurine compound of formula (I), which can be difficult to filter, and avoids the problems associated with handling gaseous hydrogen chloride. As a result, the process according to the present invention is a safer process in which the amount of solvent used is lowered, minimising waste and environmental impact, the cycle time is reduced, and the throughput and overall yield of the process is increased.